PRIMATE SCIENCE RESEARCH HIGHLIGHT
November 19, 1999
"Researchers find clues to mystery of AIDS virus variability"
Scientists working with monkeys at the University of Wisconsin-Madison have
discovered new evidence explaining why retroviruses such as HIV in people
and SIV in rhesus monkeys are so variable and difficult for the body's
immune system to target and kill.
The finding, reported in the November issue of the scientific journal
Nature Medicine, is another step toward the development of effective
vaccines to prevent AIDS. David I. Watkins, professor of pathology and
laboratory medicine, and two graduate students, David Evans and David
O'Connor, conducted the research at the Wisconsin Regional
Primate Research Center, one of eight U.S. primate centers supported by the
National Institutes of Health.
A key finding: Killer cells called cytotoxic T lymphocyte cells (CTLs)
likely play a greater role than previously thought in controlling infection
in both humans and monkeys, says Watkins.
"Two important arms of the immune system that respond to infection are CTLs
and antibodies," Watkins explains. "However, the antibody response does not
fully develop until much later. By contrast, the peak of the CTL response
coincides with early control of virus replication."
Within a month after infection, he says, enormous replication takes place.
The virus infects and then copies itself within host cells, turning the
host cells into "virus factories." CTLs recognize these infected cells and
destroy them, limiting viral spread.
Unfortunately, although a strong CTL response arises early, it ultimately
fails to prevent progression to AIDS. Previous research has implied that
HIV escapes the CTL response by replacing specific amino acids within
regions of its own proteins that would normally be recognized by CTLs. The
researchers tracked 10 of these regions, called epitopes, during the course
of disease progression in rhesus monkeys. All 10 epitopes accumulated amino
acid replacements. Many of the replacements either reduced or eliminated
the CTLs' ability to kill virus-infected cells.
"This supports the CTL escape hypothesis and underscores the importance of
these killer cells in controlling viral replication," Watkins says.
Further characterization of CTLs and the epitopes they recognize is
critical to designing effective vaccines, he added. The Wisconsin Regional
Primate Research Center is now developing a colony of genetically defined
rhesus monkeys for more controlled AIDS research.
The Nature Medicine study represents collaboration between Watkins and
Alessandro Sette at Epimune, Inc., of San Diego, Calif. The work also
involved the Laboratory of Genetics and Department of Pathology and
Laboratory Medicine at UW-Madison, Biomedical Primate Research Centre-TNO
in the Netherlands, and the Institute of Molecular Evolutionary Genetics at
Pennsylvania State University.
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Reference:
Evans, D.T., D.H. O'Connor, P. Jing, J.L. Dzuris, J. Sidney, J. Da Silva,
T.M. Allen, H. Horton, J.E. Venham, R.A. Rudersdorf, T. Vogel, C.D. Pauza,
R.E. Bontrop, R. DeMars, A. Sette, A.L. Hughes and D.I. Watkins. 1999.
Virus-specific cytotoxic T-lymphocyte responses select for amino-acid
variation in simian immunodeficiency virus Enf and Nef. Nature Medicine.
November. 5:11;1270-1276.
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Primate-Science Research Highlights appears every other week and focuses
broadly on research involving non-human primates. Coverage includes
biomedicine, behavior, conservation and veterinary science. Please
submit highlights for this column to Larry Jacobsen, Primate-Science Research
Highlights editor, at jacobsen@primate.wisc.edu. A 300-word limit and
lay-language style are recommended. Primate-Science Research Highlights are
supported by a grant from the National Institutes of Health,
National Center for Research Resources. Copyright 1999,
Wisconsin Regional Primate Research Center. No portion of this highlight
may be copied or redistributed without the consent of the editor.
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